The overall goal of this project is to develop a novel antibody-based therapy for HIV infection. We anticipate that metric tons of the unique, proprietary humanized anti-CD4 antibody hu5A8 will be required to address the global AIDS pandemic. Therefore we seek to express hu5A8 in transgenic plants. Transgenic plants are expected to deliver antibodies at a fraction of the cost of fermentation as current levels of production exceed 5 kg/acre. Targeting CD4 is advantageous because CD4 is a host cell protein that does not mutate compared to HIV antigens gp120 and gp41. Furthermore, GD4 is the primary receptor for HIV, in contrast to the multiple redundant chemokine co-receptors. Alone Hu5A8 is at least 100x more potent than the best available anti-HIV-1 neutralizing Mabs (eg. 2G12, 2F5, and b12). Preclinical animal studies are promising as Hu5A8 reduced proviral load in SIVmac-infected rhesus monkeys without demonstrated side effects. After 6 weeks of repeated administration of the antibody. the rhesus monkeys had no evidence of lymphocyte dysfunction, lymphocyte depletion or immunosuppression (Reiman et al, 1997). In phase I we will a) prepare hu5A8 IgG4 plant expression constructs; b) transform tobacco, select plants expressing high levels of assembled anti- HIV IgG4 and purify hu5A8 for pre-clinical studies; and c) evaluate in Vitro binding and anti-HIV neutralizing activity of purified hu5A8 plantibodies. Phase II will focus on studies to support submission of an IND. Hu5A8 is a promising therapy for HIV infection. PROPOSED COMMERCIAL APPLICATION: The market for an effective agent for HIV infection is substantial.